Why Progesterone Is Both Good and Bad for Mood (and How to Treat PMDD)

Progesterone calms the brain and promotes sleep. At the same time, progesterone seem to play a role in the mood symptoms of premenstrual dysphoric disorder (PMDD).

How can both things be true? The short answer is that progesterone is usually good for mood but can sometimes be bad.

Keep reading for the longer answer about progesterone and mood.

Contraceptive progestin drugs are bad for mood

Progestins are not the same as the body’s own progesterone, so they shouldn’t come into this conversation. Unfortunately, many doctors, journalists, and even scientists confuse progestins with progesterone and so say “progesterone is bad for mood” when they really mean progestins are bad for mood.

Contraceptive progestins such as levonorgestrel, drospirenone, and norethisterone have been linked with anxiety and depression, but mood symptoms from birth control are drug side effects, not PMS or PMDD.

Progesterone and the brain

For most women, the body’s own progesterone is soothing because it converts to a neurosteroid called allopregnanolone which calms GABA receptors in the brain.

Progesterone’s neurosteroid effect is why we feel sleepier during the luteal phase and pregnancy. It’s also why natural progesterone capsules are part of my “rescue prescription for perimenopause and menopause.” We don’t get the same soothing effect from contraceptive progestin drugs because progestins do not convert to allopregnanolone.

For a small number of women, allopregnanolone does something different at the GABA receptors. Instead of calming them, it produces intense anxiety and other mood symptoms, which is called premenstrual dysphoric disorder or PMDD.

Women with PMDD have the same amount of allopregnanolone as other women; they just respond to it differently. In particular, women with PMDD have a reduced ability to adapt to the normal ups and downs of allopregnanolone because their GABA receptors have a reduced ability to reshuffle their five subunits.

A GABA receptor with its five subunits, and showing where GABA and neurosteroids bind.

Normally, the subunits of the GABA receptors mix-and-match throughout the cycle to reconfigure the shape of the receptor and adjust its sensitivity to fluctuating levels of neurosteroids. It’s hormonal resilience in action.

If GABA receptors cannot reconfigure their shape or adapt to fluctuating progesterone, the result is what researcher Tory Eisenlohr-Moul calls “neurosteroid change sensitivity” producing the mood symptoms of PMDD. I am following the work of Dr. Eisenlohr-Moul with great interest, and if you want to hear more of Dr. Eisenlohr-Moul’s thoughts, please scroll down and read her very helpful comment under this blog post. (Shared on April 23 at 11:40 am.)

👉 Tip: For many of my patients, avoiding cow’s dairy is the simplest way to reduce a mast cell or histamine response. Another potentially beneficial effect of avoiding dairy is to reduce exposure to a casein-derived neuroactive peptide called BCM7, which affects levels of GABA.

👉 Tip: The therapeutic dose is 300 mg of elemental magnesium, so please read the label. Most magnesium capsules are about 100 mg magnesium per capsule, so the dose is three capsules.

Vitamin B6 (pyridoxine), which assists in both the manufacture of GABA and the healthy clearance of histamine. The therapeutic dose is at least 50 mg pyridoxine or pyridoxal-5-phosphate, but I sometimes prescribe more to be taken during the days of mood symptoms. Consult your practitioner because long-term high-dose vitamin B6 can cause nerve damage.

Natural progesterone capsules because a higher external dose of progesterone can relieve the PMDD symptoms caused by fluctuating moderate levels of internal allopregnanolone. The explanation is an apparent “bimodal association between serum allopregnanolone concentration and adverse mood” which means that GABA receptors respond better to a higher steady-state level of allopregnanolone than they do to a lower fluctuating level.

For mood and sleep, 100 mg progesterone capsules (such as Prometrium) work better than progesterone cream because oral progesterone converts more readily to allopregnanolone.

Milder PMS symptoms

Milder premenstrual symptoms (PMS) that occur only during the last few days of the cycle are not the same kind of neurosteroid sensitivity as PMDD. Instead, they are simply withdrawal from allopregnanolone. PMS responds to many of the treatments listed here as well as those in my histamine and PMS post.

106 thoughts on “Why Progesterone Is Both Good and Bad for Mood (and How to Treat PMDD)”

Hello Dr. Lara, Thank you so much for all of this wonderful information, thank goodness for you help with all of this! I just recently turn 44, I had two miscarriages last year (no previous pregnancy) . I was having trouble with my hormones, energy, UTI’s and weight gain. I found a great doctor for bio-identical hormones and he put me on “mild doses” to help. I am taking 50 mg of progesterone every evening and 10ml of testosterone every morning. I feel great and my health and self have returned to normal so its working but I have one concern…..everything I read says take Progesterone on a cycle, I am the only one I know who takes it daily. I still have my monthly cycle. Just wondering your thoughts please? Thank you!

I had been casually given a fast diagnosis of PMDD about 3-4 years ago, and offered to take an SSRI. I have never done so. Things that have helped me: 1. Glycine probably becuase of it’s support of methylation (I have histamine intolerance) and because of the reasons Dr. Lara Briden recommends it as magnesium glycinate. 2. lowering histamine in general (I didn’t know this at the time. I was just trying to lower histamine symptoms and heal from histamine intolerance, but in retrospect, getting it very low has really helped my mood and the “PMDD”) 3. After much reading of Joan Mathews Larson and Julie Ross’ The Mood Cure https://www.juliarosscures.com/mood-cure/ plus The Chemistry of Joy and Dr. Mark Hyman’s Broken Brain book and docuseries… I decided to take 5htp. I really noticed the difference at first and continued. Worked with my ND and she is a fan of 5htp and as a result I upped my daily dose, which I spread out over 3 x per day. I am considering switching over to Griffonia simplicifolia seeds now that I am feeling very emotionally stable.

I was using progesterone cream for about 6 months before I went on the oral progesterone just 2 cycles ago. When I started the progesterone cream, I got tender breasts at first, and after a few months the breast tenderness was either gone or it would sometimes only occur close to the end of my cycle. If you haven’t been on it for a few months, why not stay on it and see if things level out for you? I don’t know about the weight gain because I’m 45 years old and I can’t tell what’s making it difficult to lose belly fat–but, I know I have to eat less than I used to and that seems to be the general consensus among people my age. I am doing the dietary advice from amongst the functional medicine doctors who write on the internet and books (intermittent fasting, restrictions, Paleo, Wahls protocol, etc.). I hope Lara catches your question on whether it’s good for you to be on the oral prog. with the endometriosis. Have you read her book?

My integrative health practitioner prescribed me 100mg capsules of progesterone. The result is significant breast tenderness and enlargement and almost immediate weight gain around my stomach (which I’ve not had before). Is this normal? The weight gain and breast tenderness (and noticeably larger) is making me self-conscious and unhappy. Do the benefits outweigh the side effects? I have endo and excess estrogen.

Lara, I love that you are so open to learning from others. Your curiosity is admirable. When should one dose progesterone cream? I’ve been splitting my daily dose morning and evening, but this makes me wonder if morning would be best?

I am on second cycle using oral progesterone. I stop it on Day 24. I feel like my mood was bad from stopping the progesterone. Is there any way around this? We have to stop the progesterone to mimic the natural drop in progesterone, but whether it’s from natural or a pill, the drop in progesterone causes me to have a bad mood. Do we just deal with it because “it’s natural”?

Would like to know more about the timing of taking oral progesterone. This article says:

“Take Hormones Once a Day in the Morning by Joseph J Collins, RN, ND

Your body makes testosterone, progesterone, estrogens, DHEA, cortisol, thyroid hormones, etc., on a 24 hour basis. The science on this is indisputable. So, twice a day dosing is one of those things that have become common practice, even though twice a day dosing is not grounded in good science. Your hormone levels are naturally higher in the AM and lower in the evening. The drop in hormone levels at the end of the day actually signals the body that it needs to make “another batch” of hormones. The daily cycle of hormone production is described as a “circadian” rhythm – a 24 hour rhythm.

The daily high and low values both signals the need for more hormone production, and help decrease the risk of developing hormone resistance – a situation where the cells of the body become resistant to hormone messages because the hormones do not drop as they should.

If hormone levels do not drop, and send too strong a signal – like they are yelling at the cells all the time – then the cells start to resist the hormone message. If some of these hormones are too high in the evening, they interfere with the release of night-time hormones. Elevated evening estrogens interfere with growth hormone release. So, it does not make sense to take estrogen twice a day if a woman wants her skin to stay young and healthy.

More detail and references are included on page 277 – 280 of Discover Your Menopause Type.

And yes, some women are given progesterone at night to help them sleep. This means progesterone is being used as a sleeping agent. Does it work? Apparently it does. But using progesterone this way is counter to the design of the body because progesterone is naturally higher in the morning. There are other ways to restore healthy sleep. ”

Interesting. He doesn’t actually specify which night-time hormones are triggered by the drop in progesterone. Do you know if he specifies it in his book? It is an interesting argument for morning dosing but oral progesterone makes most women so groggy that I would be reluctant to recommend that.

Hello Lara! I have endometriosis and was not wanting to go back on the pill (my gyno’s only option for me besides surgery) so after reading tips from your book I was able to lower my pain and correct my low progesterone by supplementing with b6, magnesium, and zinc. So my endo pain (which was literally ruining my life- could not function for half my cycle) has gone down from a 8 to a 2, but my Pmdd which was diagnosed at 15 (im 32) has gotten SO MUCH WORSE with these supplements as the endo has gotten better, so it seems to clearly be the progesterone. Like i am totally miserable and angry for a week to ten days before my period. Feeling like I can’t win and have to choose between pain or mental health. I went off the pill 3 years ago bc of high cancer risk and it aggravating another autoimmune disease. Any Suggestions?

Hi Rachel, I am glad that you found a solution, even if it`s partial. Could you please share the name of your naturopath? And yes, I`ve read in multiple sources that there`s a strong connection between vlood sugar and mood. Thank you very much!

Try the book Magnesium Miracle by Carol Dean. I have stopped using Epsom Salt baths as a routine and am now using Magnesium Chloride spray “oil” and also lotion. It has really helped with the muscles around an injury. I seek to get magnesium in diversified ways.

Would there be a hormonal reason oral Prometrium at 100mg daily would cause intestinal pain or distress? It has helped my mood and sleep, lessened my period, but now in my second month of taking it I am nauseous and my whole intestinal track is irritated or cramps.

I just started oral bioidentical progesterone. Doctor said take it on days 12-24, but stop at the first sign of any pink (even very little flow, which is Day 1) even if that occurs before Day 24. .But doctor said for my cycle being typically from 23 days to 26 days, take the oral tablets on days 12-24 because if I take them past day 24 I could lengthen my cycle too much. I’m concerned about the drop in progesterone on Day 25… For PMDD isn’t this also yet a different way to end up with a drop in Progesterone?

What I am personally doing right now, as part of a larger nutrient supplementation plan, is to take the B6 and mag every day. B6 helps with histamine (I have histamine intolerance, and as I’ve gotten histamine under control, what I thought was PMDD is now much more mild. I’m taking magnesium because of book by Carolyn Dean, MD, ND. I am adding the taurine next, to calm GABA receptors in general, improve insulin sensitivity, and because it’s safe to take every day at a lower amount (see Examine.com) Dr. Sarah Gottfriend also likes taurine and has put it into her “Crave Control” formula.

Lara, I’ve read your book a few times and appreciate the information you’ve provided to women. After reading, I started taking magnesium, B6, and Taurine. I’m unsure on how I should take them though. Should they be taken daily or only during the luteal phase? Also, should they be taken in the morning or at night? Finally, would a PMDD sufferer benefit from Omega 3 supplement in addition to the supplements above? Thanks!

Hi Dr Briden! I have one question. I am taking cerazette and noticed an increase in body hair since I switched from the combined pill to the progesterone only pill. I am wondering if the progesterone (or better saying progestin. In this case desogestrel) in this pill could actually contribute to increased body hair. I have been to several gynecologists, endocrinologists and dermatologists and they all ignore my complaints and tell me to accept that I’m hairy and it’s probably just genetics

Talked to my (awesome) doctor about it today and think I will do that. It seems to be very good for so many reasons for me. Thank you for introducing me to progesterone and allo and also the idea that “women are not small men” – went to a neurologist and not once was asked if I felt my seizure and other temporal lobe epilepsy symptoms were exacerbated by my cycle – when it turns out that in many women with epilepsy it is a studied and important factor (and are also more likely to have anovulatory cycles).

I am into my second month of taking natural progesterone and I love it. But perhaps too much. For the first time in forever my sleep is restful – I have sleep apnea and epilepsy (perhaps catamenial in nature) and wondering if it is providing a solution to both of these things with progesterone being a respiratory stimulant and allo being anti-seizure The problem is that I want to take natural progesterone in the first half of my cycle because I know what it can be to switch off my short circuiting brain and rest now. Looking into other ways in how allo can be boosted besides SSRIs as they do not agree with my sensitive brain chemistry either.

Thanks, Dr Briden! I think I’ve exhausted everything on Dr Prior’s website (so helpful) and was planning to order her book for an upcoming plan ride 🙂

IIRC, I think she definitely favors daily dosing for those with migraines (which I don’t have).

If one were to start out with dosing during the second half of the cycle only, what symptoms would indicate that perhaps daily dosing is a better option? Guessing they overlap with symptoms that indicate that progesterone isn’t the correct treatment – period?

Being perimenopausal w/out a uterus is so difficult, as most doctors keep telling me that I don’t need progesterone without one 🙁 And as someone with endometriosis as well, I don’t feel comfortable with the estrogen only treatment plans.

The “progesterone” the doctors are talking about is actually progestin. Most doctors seem to have no clue about the value of real progesterone for perimenopausal symptoms and general health. And so they say it is only to protect the uterus from cancer. When, in reality, it does so much more!

Question: If one is sensitive to the ups and downs of progesterone (as mentioned towards the end of your article), is perimenopausal, and has had a hyst but spared ovaries, is it better to dose 2nd half of cycle only, or daily?

In most cases, I think the last two weeks of the cycle is the best dosing but I know that Professor Prior (author of the perimenopause book Estrogen’s Storm Season) makes the case for daily progesterone. I’m just reading her book again now.

I have been struggling for the past year and a half (been on birth control for only 2 years) with PMDD-like symptoms due to my birth control pill (i am currently 19 years old) switched my birth control pill 3 separate times and also tried two SSRIs and nothing helped. currently i have been taking loestrin fe every day with no inactive days for the past two months per my gyno’s recommendation saying it should be an easy fix. my depressed moods have gotten better but the anxiety still breaks through, i don’t feel like myself. i have a doctors appt in 2 weeks & i plan on going off the pill & trying natural solutions. going to order your book to help along with the process. i am sick of feeling like i am crazy!!

I would also like to mention that i have had anxiety and depression for 4 and a half years and there was no clear pattern of pmdd symptoms until a year and a half ago (i know its different if they show up after being on bc) but also my mom had pmdd so it runs in the family

Short answer, no. There’s no clear relationship because PMDD is defined as mood problems that occur after ovulation. With true PCOS, there is no ovulation, and therefore no possibility of PMDD.

That said, women with PCOS can definitely experience mood symptoms, especially once they start to ovulate again. I see that with my patients with the inflammatory type of PCOS. When they reestablish ovulation, they can start to have mood symptoms. The treatment is the same: to reduce inflammation and histamine.

I’m looking to reverse my hormonal issues while trying to conceive my second child again. Background info I’m 28, 5’3 142 pounds, married with one child she was born at 25 weeks due premature rupture of my membranes but she has no major issues thank God! I have never had acne, but I have always been hairy everywhere (I was also born premature at 26 weeks and they had to give me steroids as a baby) I was recently diagnosed with PCOS again this year and I was told (I have a copy of the test results as well) by my obgyn that I had high levels of Androgens and my thyroid levels were a little high. He did tell me to make a few changes in my diet and start exercising and it’ll be reversed.

I did have low progesterone and was prescribed prometrium while I was pregnant but I stopped taking it. Would this be something I can take as a cream or pill form along with continually eating healthy, exercising and of course not stressing to balance my periods and prevent another preterm labor?

Also would spearmint tea lower my androgens which will in turn slow down the excessive hair growth?

Hi Lara, my periods have been very out of whack since having my youngest son 3 years ago. I originally went on the pill but came off after about 6 months due to migraines. ever since I have a cycle length of between 30 and 35 days, my menstruation is 3 days of medium flow then 7/8 days of on and off spotting. From researching online it seems as though I have hormonal imbalance, which isn’t helping me with trying to conceive. After 8 months of trying, I fell pregnant in December (after taking Agnus Castus Vitex up to ovulation for one cycle) and I then miscarried in February at 11 weeks, it completely devastated me and I’m now finding it very difficult to fall pregnant again. Is there anything that I can do to help with my hormones so that I can conceive again?

Hi I was diagnosed with adrenal fatigue 2 years ago. I did a salivary adrenocortex 4 point test with sex hormones. Cortisol was flat lined, progesterone low, DHEA low and estradiol high. I took calmx, Plift, i3c, adrenotone and bio identical DHEA solidly for 8-9 months. Along with iron for anemia. My iron levels were very slow to come up due to I suspect the heavy periods I was having. In an attempt to reduce the bleeding I started on bio progesterone cream and only managed to take it for about 6 months. It initially helped with some pms symptoms but didn’t significantly reduce bleeding but did however reduce my cycle length to about 21 days. I’ve been off the progesterone for about a year now and my cycle has slowly crept up to about the 25 day mark but is a little irregular now which has never been an issue previously. I’ve read your book and I suspect I am either not ovulating or producing enough progesterone but I’m confused as to why the progesterone cream didn’t help me? Please help. One very confused.

I am about to come off the pill in 3 days time and a bit worried about the mental heath effect it might have? I am on an SSRI (problems may have been caused by the pill all along) but I am hoping that because of my proactive steps (adding Magnesium and Zinc) and the reintroduction of my own natural and calming progesterone, I will feel even better than on it! Any other suggestions to assist with balancing of mood during the transition?

Hello!!!. I just read your book period manual repair and I liked it a lot. I suffer from menstrual migraines and they recommended the Tanacetum Parthenium as a preventive. In your opinion, do you think it is effective? I’m starting to take the food issue more seriously and even though I was already eating very little sugar, I’m going to try to eliminate it completely. A greeting from Spain!!!!!

Hi Dr Briden, thanks for your response to my comment above. I am going to try mag, b6 and taurine and have checked out this brand on amazin UK. The label isnti entirely clear in that it states each tab contains magnesium (glycerophosphate, carbonate) 87mg/23% EC RI, so I assume that means I’d have to take 4 tablets per day. My concern with that is in doing so, am I under or over on the other two elements? The label states each tablet contains 150mg of taurine, and 2mg VB6 pyridoxine HCI, so presumably the latter falls incredibly short of your recommended dose of 50mg and as such, would it make more sense to go with separate supplements for each?

Also, with regards to levels of histamine, would the effects of short terms use of anti-histamines be indicative of whether or not allergies are a problem for me? I used to suffer incredibly badly with stress triggered hives, or so I thought, but now wonder if hormones were the trigger instead. Fortunately, I no longer regularly experience these breakouts.

Thanks in advance for any further advice you give, I appreciate that you must be incredibly busy. Kind regards.

Lara, great article. I only recently started with PMDD severe hormonal symptoms after my doctor put me on Lexapro last year after my mom’s death. I never had these PMDD symptoms before, but something switched in my body? IDK. Lexapro made me feel worse and only exacerbated my anxiety and panic attacks. Hence I came off of it. I’ve been attempting to deal with PMDD now for the last 3 cycles based on your recommendations of magnesium, VB6, iron (my ferritin was 50), bioidentical progesterone cream. I also am using L-Tryptophan since my serotonin levels are very low based on symptoms. I tried 5-HTP but that may me feel unbalanced and gave me knots in my stomach. The tryptophan does make me feel better.

I feel some improvement with my symptoms using vitamins & minerals. I tried the Vitex and that made me feel worse. That was a BAD reaction; couldn’t leave my bed all day. My quesiton is this, what do you recommend for my EXTREME ANGER? This past cycle when I got my period — I was a lunatic! I lost it at work (surprised I’m not fired yet because of PMDD) and at home the anger was so severe I was breaking & smashing things in my apt. Yikes! I feel like Dr. Jekyll & Mr. Hyde… it’s so not me but the worst comes out. I’m desperate – I’m trying everything. My GYN wants to put me on birth control but as you state Ode to Ovulation! So I said no. Help!

Hey Natalia, sorry for your loss. I suffered really similar symptoms every month too, mine was from coming off the pill after 13 years. Replace extreme anger with extreme depression and anxiety (to the point I was crying hysterically for a week and couldn’t leave the house). Then once my period arrived I was back to my normal bubbly self. It’s like flicking a switch, I felt like every doctor I saw thought I was just depressed and tried to prescribe me antidepressants and counselling, but I was honestly fine the first 3/4 of the month and felt there was more to it. After seeing a naturopath for advice – I found I felt my best when I was eating organic food, no dairy, no processed food or sugar, increased my water intake and joined a fitness class, I also took Vitex and a B12/magnesium supplement and Probiotics (for gut health) and completely cut out alcohol (I’m not much of a drinker anyway, but alcohol can understandably affect your hormones). It took about 3 months to notice a change for me. I would highly recommend seeing a naturopath for guidance on supplements etc. I hope you feel better really soon, you’re not alone 🙂

Hi, please could you suggest a brand that would deliver the required amount of elemental magnesium? I’d also be interested to try progesterone tablets for migraines – would this be on prescription only? thanks in advance

I had a chance to finally get and read your book, what a wonderful resource for learning about our own bodies! I do have a question on units, in the book you mention that a mid luteal progesterone reading of atleast 3 ng/mL is required to point to ovulation having occured. I just want to make sure that is serum progesterone and not saliva? Also is ng/mL or ng/dL? I had both saliva and serum tests done and the saliva test is showing VERY different readings so I wanted to double check.

Hi Dr Briden. Your article has given me lots of new possibilities for alternative treatments, thank you. I’m in the UK, have pmdd (onset at ovulation, day 8 of cycle, and would last until my period started). Symptoms range from severe depression, suicidal ideation, painfully sad, very emotional, sensitive to noise, joint pain. My Dr is very nice, and is open to me making suggestions about treatment.

I have been on two different SSRIs over many years, and honestly, when PMDD symptoms begain, it’s like they cancel out the effects of the SSRIs.

My Dr asked me to try a contraceptive pill, the first of which made me worse. The second (yaz/eloine back to back) has helped, but I still do experience some lows which appear to be random, so I asked the question of the IAPMD foundation as to whether or not taking the contraceptive pill back to back means ovulation stops altogether, but they weren’t able to answer.

I’m now at the point where I really want to stop taking both the contraceptive pill and SSRIs, but am afraid that doing so will set me back drastically. For the last three months or so, I have supplementing with magnesium oil and magnesium chloride flakes which has remedied my RLS. I decided to go transdermal because I have stomach issues. However, I recently read that taking lansoprazole could be affecting my liver function which I guessed would be affecting hormone elimination, so I stopped that, and started apple cider vinegar and collagen powder which has sorted out my leaky gut, and I instantly lost 6lbs in weight. I’ve recently started a super-B complex, but I’m only getting 20mg of b6 daily, so need to address that. I’m now keen to try taurine after reading your article, but I’m concerned that while I’m taking the pill and SSRI, the supplements won’t be as effective as they could be. I wondered if you could give me your thoughts please? Apologies for the mammoth comment, I’m just so desperate for some relief, and unfortunately in the UK, there is only one clinic that specializes in pmdd and it’s in London which is at the opposite end of the country from me. Thanks in advance.

As I explain in the post, mood symptoms on the pill are drug-side effects, not PMDD. And possibly will not respond to the treatments that I recommend for PMDD. So, correct, “the supplements won’t be as effective as they could be for the mood symptoms of a natural cycle.”

And in answer to your question about ovulation, the pill (in any dosing) suppresses ovulation. There has never been any reason to bleed monthly on the pill. (ie. it’s just a drug-withdrawal bleed, not a cycle).

Hello, I have had PMDD my entire reproductive life and it seems doctors are just recently starting to understand it as I was usually met with puzzled looks by my OBGYN and nurses when I complained of my symptoms. I am on an SSRI which helps some but I have been trying to taper off of it as I may become pregnant in the next year. Given this logic of progesterone sensitivity, would you recommend trying Vitex supplements? I took it for a few days but it seemed to make my mood symptoms worse. I know it supposedly increases progesterone. Thank you

Thank you so much for your informative articles. I had a DUTCH hormone test done, and found that (amongst many other things being amiss), I am actually having HIGH progesterone during the later part of my cycle (and a cycle that can last multiple months), along with the same PMDD symptoms that seem associated with low progesterone (and I have now begun experiencing the same or similar PMDD symptoms, plus extreme fatigue, earlier in my cycle too. Is this anything you have any knowledge on? Thank you! It is debilitating right now, and seems to be getting substantially worse, every cycle.

When you say “a cycle that can last several months” do you mean three months between bleeds? in that case, you’re either not ovulating (anovulatory cycle — read 3 signs your period is not really a period) or your luteal phase is only the final 12 days or to before your period actually arrives. Is that when the test was done?

Regardless of how long a cycle is, we can only make progesterone for the final 12-14 days.

And as for the DUTCH high progesterone reading… A patient once brought a similar high DUTCH test high progesterone reading to me, and we found that it did not match her serum reading and it made no sense clinically so I just disregarded it.

Yes, when I initially had an iron panel done my levels were low so I started a supplement. My repeat levels were normal. It’s more than fatigue for me. It’s crying, hopelessness and feeling completely worthless from pretty much day 1 of my period until right around my basal temp shows ovulation. Right around that time it’s literally like a switch goes off and all those awful feelings float away. I feel great the rest of the month, like my normal self. I just feel like something is out of balance but I don’t know how to fix it.

thanks so much for sharing your story. I have not encountered a similar situation with patients. Also, what’s interesting is that day 1 and ovulation are very different times hormonally. So, from a hormonal perspective, I’m not 100% sure what could be going on. Happy to have anyone else chime in here!

Wow, this is an eye opening and interesting article, Dr. Briden. Thank you! I fit this paradox somewhat. My saliva hormone test (in luteal phase) showed low-ish progesterone and high estrogen (ratio was off). My doctor has been treating my high estrogen with DIM and Calcium D Glucarate for about a month since the test, and just last week she gave me a prescription for progesterone cream 10 mg because I complained of water retention in the face which subsides by the evening. I applied the progesterone cream before bed and experienced terrible hot flashes, racing heart beat, sleeplessness, agitation and the next morning I had severe brain fog and a very unsettling, floating feeling. I stopped the cream and within two days the symptoms went away. Is it possible to test low on a saliva test and still have a sensitivity to topical progesterone? I was expecting the opposite result and I am a little shocked. As a side-note, I have extremely easy, regular periods 31-33 days apart, no PMS or pain, normal bleeding and lasts about 4 days. I am starting to think the saliva test might be erroneous and I need a serum test instead? Any thoughts/guidance would be greatly appreciated!

Hi Kelly, I am this way too. I used to be PMDD but I am realizing now that the real dip happens throughout my period. I get so weak and depressed. It’s debilitating. I wonder if the recommendations in this article apply to people like us too?

What about mood symptoms that begin AFTER your period? I have noticed recently this trend that my mood and energy levels are extremely low (like depression level low) from the start of my period until around the time I ovulate – the opposite of what everything tells me I should be feeling at this time of the month. I am 32 and have no other health issues. Rarely sick and I’ve never even had a headache in my life. I have a very regular cycle which I track with basal temps and the help of two apps. I’ve never used any hormonal birth control. “Typical” PMS symptoms are generally mild and have improved even more since I started taking magnesium glycinate that you recommend. I eat a healthy and varied diet and have never had weight issues. Very little dairy. I talked to my doctor and had my hormone levels checked a few months ago. Everything was within range but I still feel like something is off. Every month I just wait for mid-cycle to come around so I can feel better, normal and happy again. Any ideas? I hate feeling like this 🙁

I had vaccines for multiple allergies for 5 years in my childhood. I read your article about histamine and estrogen, posted about endometriosis and antiphospholipid syndrome and it all started to make sense. I noticed that the pain is worse and all the complications appear in March – April, every year, when I also have allergies, but in winter I feel better – often on antibiotics, sick. My mother had endometriosis, multiple allergies and histerectomy when she was stage II endometriosis – 40 years old. I’m 30, stage IV endometriosis and had one laparoscopy. I would like to postpone Diphereline as much as possible. I’ m going to try again your treatment and I wonder…should I treat autoimmune diseases or allergies? Plaquenil or Xyzal …or berries, natural methods, natural cortisone? What do you think about natural blood thinners? What do you recommend? Thank you very much!

I have not been diagnosed with APD but I do have PMDD and I used to have terrible urticaria which always flared up around menstruation. I had to take an anti histamine every single day, sometimes twice just to make it bearable. Also caused classic dermatographia – I could literally write my name on my arm with my nail. Once I got pregnant, the urticaria and dermatographia stopped completely. I knew it was hormone related but I didn’t have the knowledge I do now! PMDD is now my biggest battle (BTW I had endometriosis in my mid 20s (now 36))

Thanks Lara I would prefer Prometrium so will continue to request that instead, I was so confused when they said a troche instead. I’m disappointed a clinic that specialises in women’s hormones would be saying this to their clients though. The prometrium side effects report on hepatoxitcity so maybe they ran with that but I couldn’t find any articles on prevalence either way though. Thanks again

Thank you so much for this info! I’ve been following your work for a long time dealing with PMDD. For the last 3 months I started developing autoimmune progesterone dermatitis- an annoying and irritated rash in my left armpit and sometimes vestibulitis (during luteal phase at random months for the past 6 years). I always thought I had estrogen dominance because of my sluggish liver. I have histamine like reactions to alcohol – sinus inflammation, terrible migraines and mast cell degranulation attacks. Wondering if high estrogen leads to high progesterone- this the autoimmune reaction? I’m already aware of how bad gluten and alcohol worsen the autoimmune response and just started a vegetarian diet 2 weeks ago- UFF DA- looks like I should quit dairy too! 🙁 Anyway that’s a super brief testimony to progesterone intolerance coming from someone with PMDD and autoimmune progesterone dermatitis. If you have a protocol on how to deal with this- I’d be all over that!

Interesting. This is the second comment about autoimmune progesterone dermatitis on this thread. Makes me wonder if maybe it is more common in women with PMDD. And if there is some link. In my previous response, I said that autoimmune progesterone dermatitis is a different kind of progesterone sensitivity, related to the immune system rather than the GABA receptor. But of course, the immune system could be involved in both.

Also, for what it’s worth, I’m really not a fan of a vegan diet. Mainly because it’s deficient in zinc and taurine and vitamin B6 — all so important for mood.

Hi Lara, Would natural progesterone (such as HRT cream) also cause Neurosteroid sensitivity? Or would only be caused/triggered by our own progesterone? I have endo and perimenopausal and was prescribed by my ND a natural compounded progesterone cream but sometimes I have noticed mood changes when I take it. I suspected it had to do with the progesterone but it could be other factors as well. As I read your article, it made a lot of sense for me! Thank you, Cristina

Hi Lara I recently visited a natural women’s hormone clinic – I have endometriosis (now excised) and adenomyosis. I’m getting my hormones tested on day 21 of my cycle as requested by them. I asked about prometrium being prescribed. He said they prefer a progesterone troche as prometrium is harder on the liver? Do you have any information about if troches are as good? Or why he is saying this about the liver? I’m so confused as I asked about prometrium as per your recommendations but they are telling me not to? It’s a natural health hormone clinic with integrative GPs and naturopaths. Thanks Lara

Thank you!!! I also posted there. I like your articles and I tried the treatments. Could you tell me how to take Prometrium? Maybe it wasn’t enough…or the NAC dose for optimal effect? I have constant high ESR -inflammation and recently diagnosed with antiphospholipid syndrome. Estrogen and progesterone – ok. Selenium and magnesium somehow alleviated my migraines during summer. Would you recommend something for horror pain, please? Endometriosis stage IV- nerve pain

The issue is that glycine is the bulk of the total mg count. So, 1000 mg of magnesium glycinate contains only 100 mg magnesium. Most labels include the total (~1000 mg) plus the amount of elemental magnesium (~100 mg per capsule typically).

Please keep 5htp supplementation on your radar. I didn’t want to go straight to an SSRI, and I never have because I felt different with taking 5htp. It wasn’t complete resolution for me, because there are other nutritional and psychological and lifestyle that comes into play. But 5htp, St John’s worth and SamE should be compared with SSRI eventually for PMDD. I may eventually take an SSRI, but I’m not desperate now. My Naturopathic Doctor believes most women, globally and all ethnicities, have lower serotonin as we age. She encouraged me to try a higher dose of 5htp. She even takes a high dose of it herself. Interestingly, and possibly significantly, my blood sugar seems more stable. Could blood sugar be at a root for causing or exacerbating mood symptoms? (This could be epidemic level across the population). Do SSRIs also work partially because of an effect on blood sugar?

“The amount of magnesium in Pure Encapsulations Magesium Glycinate capsule is 120 mg. The total amount of magnesium glycinate in the capsule is 1030 mg (910 mg glyinate).” From an email from Pure Encapsulations

I have histamine intolerance . But I discovered magnesium glycinate before I knew I have HI .I also resemble PMDD. what I found by trial and error is that I have a high need for glycine. When I stopped taking it, within 3 days I was back to agitated, picky, angry, aggressive, out of sorts. When I took it again, within a day I was feeling better. Now I have learned why from Chris Masterjohn PhD. Look at his methylation supplementation guidelines. I also am taking the small amounts of creatine. And some beets for betaine. And phosphatidylcholine because it has a marked effect on my cognition, brain fog, memory… Also involved in methylation.

For glycine, it works out to one capsule of mag glycinate with each meal. Or, if you want to take collagen, don’t take too much. I have recently adjusted to talking 1 tsp collagen with a high protein meal or shake. If it’s a big piece of meat, I’d do 1 tbsp of collagen. Again, guidelines are on Masterjohn’s website.

I take a lot of supplements, but for years, mag glycinate had been foundational, a lifesaver for me.

Notice how amazing the 300 mg of magnesium works out when you take 3 capsules of mag glycinate per day!!

thanks so much for sharing your story. Yes, glycine is wonderful, not just for its role in methylation but because it directly calms GABA receptors and also assists with the healthy clearance of both estrogen and salicylates.

and yes, 1030 of magnesium glycinate giving 120 mg of magnesium sounds about right. So, 3 capsules per day to get the 300 mg.

Hi, Lara! What do you think about Diphereline 3.75 mg (Triptoreline), 1/month – 6 months for inducing menopause in stage IV endometriosis? I’m 30, had one laparoscopy and recent antiphospholipid syndrome suspected. I don’t want a ” big surgery” and I’ve tried plant extracts, magnesium, B6, therapies for 15 years… What can I do to minimize the side effects? Thank you for everything!

The other treatment possibility is Prometrium. Check out Nina’s comment in this comment thread where she says: “I was finally able to get my doctor to prescribe progesterone for my endo symptoms and flooding… and it is helping IMMENSELY.”

As for “minimising” the side effects of chemically-induced menopause…there’s no easy answer. Again, progesterone might be possible, but a simpler plan would be to just try progesterone plus the zinc, NAC etc I describe in my endometriosis post. But do speak to your doctor of course.

Dear Lara, I tried a course of magnesium and vitamin B complex supplements after reading your book a few years ago, but it didn’t seem to help much with my PMS. I was glad to see your recommendation in one of the comments here for a product combining magnesium, taurine and B6 (Relax by NutriAdvanced) – and delighted to see it is available in UK. Can taking this supplement for prophylactic reasons do any harm?.. I do not think I have a PMDD, but definitely a PMS. Thank you.

Hi there! It’s great to see an acknowledgment and discussion of these important individual differences in sensitivity to hormone (and neurosteroid) changes! I have a paper coming out soon that demonstrates subtypes of PMDD– some with early-luteal-onset and some with late-luteal-onset. It’s very possible that those subtypes represent different subtypes of PMS/PMDD that could respond differently to progesterone surges, withdrawal, and supplementation. I think that more reasonable (lower) doses of perimenstrual progesterone supplementation need to be evaluated against placebo for those with premenstrual mood changes who develop symptoms late in the luteal phase (potentially in response to hormone withdrawal). I’m working on that in my clinical trials now.

A new study shows that for women with PMDD who have neurosteroid change sensitivity and develop emotional symptoms when P4 is added to GnRH agonist (ovarian suppression), the mood symptoms go away after one month of stable addback (Schmidt et al., 2017 American Journal of Psychiatry; https://www.ncbi.nlm.nih.gov/pubmed/28427285). That suggests that once the GABAARs have had a chance to adjust, progesterone and its metabolites (allopregnanolone or ALLO) are tolerable and could even be beneficial for women with PMDD.

Now, about SSRIs. People (especially in the PMDD community) love to hate on them, but there’s no denying their efficacy and first-line status in the general population of women with PMDD. Let me explain. It is true that when you’re dealing with treatment-resistant women with PMDD who spend a lot of time on the internet searching for new treatments, you find that most did not respond to SSRIs (if they did, they wouldn’t be on the internet looking for other treatments, because they’d be happy with the SSRIs). However, we shouldn’t let that biased sample fool us– a large number of unbiased, NIMH-funded (non-pharmaceutical) clinical trials now suggest that about ~60-75% of women with PMDD respond beautifully to SSRIs– it can be a lifesaving treatment for so many people (https://www.liebertpub.com/doi/abs/10.1089/jwh.2006.15.57?casa_token=OxodEFSvLBoAAAAA%3A3L5BI2JORDZeAUJxLMS0LAQuqXFiQ1lJQlp0tyWc60BvZBYgfceABHAgNc32iJHNF9ZIl6wQe4H4gw&amp;).

SSRIs don’t work for everyone, and they may have side effects (sexual dysfunction is the most common reason for discontinuation); however, I don’t agree that the link with osteoporosis is well-established (the study I found actually found that women were protected from the SSRI-osteoporosis link), and if SSRIs are a hugely helpful treatment for a given woman, bone mineral density can be easily monitored to avoid problems if someone is concerned about that. Given the severe suffering that women with PMDD often go through, often including suicidal thoughts and behaviors, and given that SSRIs are the best-supported scientific treatment for PMDD, I think SSRIs should be used as the first line treatment when PMDD is causing significant distress or impairment. They aren’t perfect, but they can be a lifesaving tool for many.

Finally, to bring things full circle: many people think that SSRIs work in PMDD in part by increasing levels of the enzymes needed to convert progesterone to ALLO; therefore, it is possible that SSRIs work for some not only due to their ability to reverse the luteal serotonergic abnormalities in PMDD, but also because they stimulate creation of ALLO (and create ALLO stability) in the brain. See here for a discussion: https://journals.sagepub.com/doi/full/10.1177/0269881113490327

Hi Lara, thanks for this post – I suffer terribly from PMDD. Before I discovered what I had – everything I read said it only affected 3% of women. Now you say it’s 1 in 20 – but I have to say that I think it affects so many more of us than that. People don’t talk about it that much and so doctors perhaps don’t hear about it. I now tell every woman who will listen about my battle with PMDD and almost ALWAYS – the answer is – “yeah me too, I have really similar problems”. Thank you for creating more awareness on the topic and for pointing out Tory’s work. I will be following it too from now on.

Love this informative article especially since I was finally able to get my doctor to prescribe it to me for my endo symptoms and flooding. However she prescribed me 200mg nightly – I saw in your earlier posts you’d recommended a lesser dose. Should I get her to lessen it. Only negative I am seeing thus far is some breast tenderness – it is helping IMMENSELY with my endo and of course the flooding. She said I’d see results right away and I am. What took them so long to give it to me!

I am familiar with Violet per your referral in previous posts. Have not tried as I’m nervous about the high dose but will discuss with my doctor. It isn’t available at any store where I live so I’d have to online order if I decide to try. I’ve had my thyroid tested and it’s in normal range but is there a specific test for thyroid other than the basic one in a general health profile? I’d love to get this breast pain under control. Thanks!

Thank you for yet another great informative article, Lara! Do you happen to know of any supplement that contains magnesium bisglycinate, vitamin B6, and taurine altogether that could be taken during the luteal phase? Particularly a Canadian supplement brand? Thanks. 🙂

I am confused about the magnesium. I thought, from previous posts and/or your book, that 300 mg of magnesium bisglycinate was a therapeutic dose and a good form of magnesium. That’s what I’ve been taking for a year or so. Is this a different dose for a different purpose?

Another informative post. When I was in my late 30s and from 40-43 or so, during what I believe was my early perimenopause, even a little progesterone did not seem to help. In fact, it seemed to make things worse. Now that I’m 46 (and think I’m entering late perimenopause), a little progesterone DOES seem to help. Is this my imagination? It seems as I get closer to menopause, things are evening out a little. However, with hormones, who can tell? : )

very interesting comment, thanks. Yes, it makes sense that GABA receptors change with age. It’s actually possible that in your late 40s you are not having ovulatory cycles so not experiencing the neurosteroid sensitivity I describe in the blog post.

Thank you for another very informative post Dr. Lara. I am currently taking 200 mg of Prometrium. I started with 100mg and my very heavy, flooding periods did not change for two cycles on 100 mg Prometrium ( in addition to magnesium and Taurine!) So far things seem better as my last cycle was manageable and a bit lighter. I was hoping the Prometrium would also help breast tenderness and swelling but so far it has not. (I’ve also tried Kelp for the iodine and it hasn’t helped either! I have a upcoming mammogram that I will have to reschedule due to breast soreness. ) Is this higher dose of Prometrium safe to take to carry me through my peri menapause? I will be turning 50 in a couple months.

natural progesterone or Prometrium is generally a very safe medication but of course, please speak to your doctor. And with regard iodine and breasts, kelp cannot provide the necessary dose. Did you see Violet’s information?

Thank you for this post, Lara! I have been wondering why I feel so bad when I ovulate, and I wonder if that is why I experienced increased anxiety when trying a small dose (<10mg) of micronized progesterone during the second half of my cycle? It really helped with my spotting and heavy bleeding, but was not good for my mood.

Anyways, given that, would it be worth it to try the 100mg Prometrium tablet? I am in very early perimenopause, and my most troublesome symptoms are insomnia, anxiety, and mild hot flashes clustered around my cycles….though the hot flashes have improved since my excision surgery for endometriosis and hysterectomy for adenomyosis, but the anxiety and insomnia have worsened. I just wonder that if a small amount = bad, does a larger amount = worse?

My second question: For my hysterectomy, I kept my ovaries. How would someone like me dose Prometrium (assuming it is worth a try)? Every day? Try to guess the second half of my cycle with temp charting??

For some women with PMDD, a small or moderate amount of progesterone = bad, but a larger amount = good. Because of the “bimodal” or “biphasic” sensitivity of the GABA receptor I describe in the blog post.

So, it’s possible the bigger dose of 100 or 200 mg would help you. There is also a chance it will not. I hope to see more research on the topic. And please do speak to your doctor about it.

And yes, luteal phase dosing would be ideal, if you can track it with temperatures.